Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth.

BACKGROUND: In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations. OBJECTIVE: We sought to identify genetic variants associated with severe asthma exacerbations in Hispanic/Latino subgroups by means of admixture mapping analyses and fine mapping, and to assess their transferability to other populations and potential functional roles. METHODS: We performed an admixture mapping in 1124 Puerto Rican and 625 Mexican American children with asthma. Fine-mapping of the significant peaks was performed via allelic testing of common and rare variants. We performed replication across Hispanic/Latino subgroups, and the transferability to non-Hispanic/Latino populations was assessed in 1001 African Americans, 1250 Singaporeans and 941 Europeans with asthma. The effects of the variants on gene expression and DNA methylation from whole blood were also evaluated in participants with asthma and in silico with data obtained through public databases. RESULTS: Genomewide significant associations of Indigenous American ancestry with severe asthma exacerbations were found at 5q32 in Mexican Americans as well as at 13q13-q13.2 and 3p13 in Puerto Ricans. The single nucleotide polymorphism (SNP) rs1144986 (C5orf46) showed consistent effects for severe asthma exacerbations across Hispanic/Latino subgroups, but it was not validated in non-Hispanics/Latinos. This SNP was associated with DPYSL3 DNA methylation and SCGB3A2 gene expression levels. CONCLUSIONS: Admixture mapping study of asthma exacerbations revealed a novel locus that exhibited Hispanic/Latino-specific effects and regulated DPYSL3 and SCGB3A2.

Tracking microbial quality, safety and environmental contamination sources in artisanal goat cheesemaking factories.

A harmonised microbiological survey was performed in two artisanal factories of raw goat milk cheeses (A and B) located in the Andalusian region (Spain). A total of 165 different control points or samples (raw materials, final products, food-contact surfaces [FCS], and air) were examined as microbial and pathogen sources of contamination of artisanal goat raw milk cheeses. For raw milk samples analysed from both producers, the concentrations of aerobic-mesophilic bacteria (AMB), total coliforms, coagulase-positive Staphylococcus spp. (CPS), lactic-acid bacteria (LAB) and moulds and yeasts ranged between 3.48 and 8.59, 2.45-5.48, 3.42-4.81, 4.99-8.59 and 3.35-6.85 log cfu/mL respectively. For the same microbial groups, the analysis of raw milk cheeses revealed concentrations ranging from 7.82 to 8.88, 2.00-6.82, 2.00-5.28, 8.11-9.57 and 2.00-5.76 log cfu/g, respectively. Although the raw material analysed from producer A presented higher microbial loads and between-batch variability, it was B the producer with the most loaded final products. Regarding the microbial air quality, the fermentation area, storage room, milk reception and packaging room were the most AMB loaded places, while the ripening chamber was the area with higher fungal loads in bioareosol from both producers. Conveyor belts, cutting machine, storage boxes and brine tank were highlighted as the most contaminated FCS evaluated. Staphylococcus aureus was the only pathogen detected within the set of 51 isolates from samples as revealed by MALDI-TOF and molecular PCR, with a prevalence of 12.5% for samples from the producer B. The public health risk attributed to the consumption of artisanal goat cheese should not be neglected, and may consider the whole cheesemaking processing chain, from microbiological quality of raw milk to the ready-to-eat final product, especially concerning the presence of S. aureus.

Prevalence of atopic dermatitis in the adolescent population of Catalonia (Spain).

BACKGROUND: Studies on the prevalence of atopic dermatitis (AD) for the adolescent cohort in general-based large populations are scarce worldwide. We performed a retrospective population--based observational cohort study of 76,665 adolescent patients diagnosed with AD in Catalonia (Spain). We studied the prevalence of AD by age, gender, disease severity, comorbidities, serum total immunoglobulin E (tIgE) and appropriate medical treatment (AMT) for the Catalan population. METHODS: Adolescent individuals (12-17 years) diagnosed with AD by medical records at different health care levels (primary, hospital, emergency) from the Catalan Health System (CHS) were included. Statistical analyses evaluated sociodemographic characteristics, prevalence, comorbidities, serum tIgE and AMT. RESULTS: The overall diagnosed AD prevalence in the adolescent Catalan population (76,665) was 16.9%, being higher for the non-severe (16.7%) than for the severe (0.2%) populations. Topical corticosteroids were the most prescribed drug (49.5%), and the use of all prescribed treatments was higher in severe AD patients, especially systemic corticosteroids (49.7%) and immunosuppressants (45.4%). AD patients had, on average, a serum tIgE of 163.6 KU/L, which was higher for severe than non-severe disease (155.5 KU/L vs 101.9 KU/L, respectively). Allergic rhinitis (15.0%) and asthma (13.5%) were among the most frequent comorbid respiratory and allergy diseases. CONCLUSIONS: This is the first Spanish study reporting the overall diagnosed prevalence for a large-scale adolescent cohort (12-17 years old) from Catalonia. It provides new and robust evidence of AD's prevalence and related characteristics in this region.

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

In vitro antimicrobial activity of extracts and essential oils of Cinnamomum, Salvia, and Mentha spp. against foodborne pathogens: A meta-analysis study.

Essential oils (EOs) are a class of natural products that exhibit potent antimicrobial properties against a broad spectrum of bacteria. Inhibition diameters (IDs) and minimum inhibitory concentrations (MICs) are the typical measures of antimicrobial activity for extracts and EOs obtained from Cinnamomum, Salvia, and Mentha species. This study used a meta-analytical regression analysis to investigate the correlation between ID and MIC measurements and the variability in antimicrobial susceptibility tests. By utilizing pooled ID models, this study revealed significant differences in foodborne pathogens' susceptibility to extracts, which were dependent on both the plant species and the methodology employed (p < .05). Cassia showed the highest efficacy against Salmonella spp., exhibiting a pooled ID of 26.24 mm, while cinnamon demonstrated the highest efficacy against Bacillus cereus, with a pooled ID of 23.35 mm. Mint extract showed the greatest efficacy against Escherichia coli and Staphylococcus aureus. Interestingly, cinnamon extract demonstrated the lowest effect against Shiga toxin-producing E. coli, with a pooled ID of only 8.07 mm, whereas its EOs were the most effective against this bacterial strain. The study found that plant species influenced the MIC, while the methodology did not affect MIC measurements (p > .05). An inverse correlation between ID and MIC measurements was identified (p < .0001). These findings suggest that extracts and EOs obtained from Cinnamomum, Salvia, and Mentha spp. have the potential to inhibit bacterial growth. The study highlights the importance of considering various factors that may influence ID and MIC measurements when assessing the effectiveness of antimicrobial agents.

Listeria monocytogenes survives better at lower storage temperatures in regular and low-salt soft and cured cheeses.

The behaviour of Listeria monocytogenes was investigated in soft pasteurized milk cheese elaborated with different salt concentrations (1.17 and 0.30% w/w) and in cured raw sheep milk cheese over storage up to 189 days at different isothermal conditions. Commercial 25-g cheese samples were inoculated with a 4-strain cocktail of L. monocytogenes (serovars 4b, 1/2a, 1/2b and 1/2c) at approximately 104 CFU/g. The inoculated samples were stored at 4 and 22 °C and withdrawn at proper intervals for L. monocytogenes enumeration. The prevalence of the different serovar strains of L. monocytogenes was characterized on soft cheese samples over storage at 4 °C using multiplex PCR. Salt reduction did not affect the survival of L. monocytogenes in soft cheeses and a maximum of 1-log reduction was observed in both regular and low-salt cheeses after 189 days of storage at 4 °C. The pathogen showed greater survival capacity in both soft and cured cheeses during storage at 4 °C compared to the storage at 22 °C, where more than 2.5 log reductions were computed. The fate of L. monocytogenes was described through a Weibull model fitted to survival data. The time required for a first tenfold reduction of the L. monocytogenes population (δ) at 4 °C is around 150 days in soft and 72 days in cured cheeses. At 22 °C, the estimated δ values are at least 60% lower in both cheese types. Among the four L. monocytogenes serovars present in the inoculated cocktail, the serovar 4b strain was the most sensitive to refrigerated storage, while the prevalence of serovar 1/2c strain increased over time in soft cheeses. Overall, the data obtained in this study help to deepen knowledge into factors affecting L. monocytogenes behaviour on cheeses and evidenced the variability between serovars in terms of survival capacity, which may be considered when performing microbial risk assessments.

Evaluation of water-assisted UV-C light and its additive effect with peracetic acid for the inactivation of Listeria monocytogenes, Salmonella enterica and murine norovirus on whole and fresh-cut strawberries during shelf-life.

BACKGROUND: The purpose of the present study was to examine the inactivation of Salmonella enterica (50 µL; 109 CFU g-1 ), Listeria monocytogenes (50 µL; 109 CFU g-1 ), and murine norovirus (MNV-1; 50 µL; 107 50% tissue culture infectious dose (TCID50 ) mL-1 ) on whole and fresh-cut strawberries after 2 min disinfection treatments (water (H2 O), chlorine 200 mg L-1 (NaClO), water-assisted ultraviolet-C (UV-C) (WUV), and the combination WUV and 40 mg L-1 of PA (WUV + PA)) in a water tank (15 L) equipped with 4 UV-C lamps (17.2 W each), and after 7 days of cold storage (4 and 10 °C). For MNV-1, dry UV-C treatment (DUV) was also tested. For all UV-C treatments, an irradiation dose of 1.3 kJ m-2 was used. RESULTS: When strawberries were washed with WUV, L. monocytogenes and S. enterica were reduced by 2.8 and 2.2 log CFU g-1 , respectively. The addition of 40 mg L-1 of PA to WUV (WUV + PA) increased the reduction range of L. monocytogenes and S. enterica by 1.9 and 0.8 log, respectively. Regarding the wash water, no pathogens were recovered after the WUV + PA treatment (detection limit 50 CFU mL-1 ). Depending on storage conditions (7 days at 4 or 10 °C), reductions observed were 0.5 to 2.0 log for S. enterica and 0.5 to 3.0 log for L. monocytogenes. The reductions in MNV-1 titer after disinfection treatments ranged from 1.3 to 1.7 log. No significant differences between storage conditions were observed for MNV-1: titers did not decline or were reduced up to 0.3 log after 7 days of cold storage. CONCLUSION: The three-way action for disinfecting strawberries by UV-C irradiation and PA, plus the physical removal of the microorganisms by agitated water, are effective against foodborne pathogens on strawberries and water wash. During storage, WUV had a larger impact on the inactivation kinetics of S. enterica. Storage had little impact on MNV-1 inactivation. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Thermodynamic Rarity Assessment of Mobile Phone PCBs: A Physical Criticality Indicator in Times of Shortage.

Rising prices in energy, raw materials, and shortages of critical raw materials (CRMs) for renewable energies or electric vehicles are jeopardizing the transition to a low-carbon economy. Therefore, managing scarce resources must be a priority for governments. To that end, appropriate indicators that can identify the criticality of raw materials and products is key. Thermodynamic rarity (TR) is an exergy-based indicator that measures the scarcity of elements in the earth's crust and the energy intensity to extract and refine them. This paper uses TR to study 70 Mobile Phone (MP) Printed Circuit Boards (PCBs) samples. Results show that an average MP PCB has a TR of 88 MJ per unit, indicating their intensive use of valuable materials. Every year the embedded TR increases by 36,250 GWh worldwide -similar to the electricity consumed by Denmark in 2019- due to annual production of MP. Pd, Ta and Au embedded in MP PCBs worldwide between 2007 and 2021 contribute to 90% of the overall TR, which account for 75, 600 and 250 tones, respectively, and increasing by 11% annually. This, coupled with the short lifespan of MP, makes PCBs an important potential source of secondary resources.

Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis.

INTRODUCTION: Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world. METHODS: REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported. RESULTS: Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p<0.001), as were those requiring hospitalisation and/or emergency department visit (from 1.14 to 0.27 per person per year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 (pre-treatment) to 5.0 mg·day-1 by week 21-24 of follow-up, sustained until week 53-56. No new safety signals were reported. CONCLUSION: These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

BACKGROUND: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. OBJECTIVES: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. METHODS: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H1-antihistamines were studied. RESULTS: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H1-antihistamines were found. CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.

Exergy Analysis of a Bio-System: Soil-Plant Interaction.

This paper explains a thorough exergy analysis of the most important reactions in soil-plant interactions. Soil, which is a prime mover of gases, metals, structural crystals, and electrolytes, constantly resembles an electric field of charge and discharge. The second law of thermodynamics reflects the deterioration of resources through the destruction of exergy. In this study, we developed a new method to assess the exergy of soil and plant formation processes. Depending on the types of soil, one may assess the efficiency and degradation of resources by incorporating or using biomass storage. According to the results of this study, during different processes from the mineralization process to nutrient uptake by the plant, about 62.5% of the input exergy will be destroyed because of the soil solution reactions. Most of the exergy destruction occurs in the biota-atmosphere subsystem, especially in the photosynthesis reaction, due to its low efficiency (about 15%). Humus and protonation reactions, with 14% and 13% exergy destruction, respectively, are the most exergy destroying reactions. Respiratory, weathering, and reverse weathering reactions account for the lowest percentage of exergy destruction and less than one percent of total exergy destruction in the soil system. The total exergy yield of the soil system is estimated at about 37.45%.

Psychometric properties of the Spanish version of the once-daily Urticaria Activity Score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (the EVALUAS study).

BACKGROUND: The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. METHODS: Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ-5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. RESULTS: Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach's alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups' validity was demonstrated by the instrument's ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7-8 points, on a scale of 0-42. CONCLUSIONS: The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version's reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS.

Impact of patient satisfaction with his or her inhaler on adherence and asthma control.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Follow-up of patients with uncontrolled asthma: clinical features of asthma patients according to the level of control achieved (the COAS study).

Our aim was to study the asthma control achieved in patients with uncontrolled asthma who had received appropriate treatment according to the Global Initiative for Asthma (GINA) 2010 (valid at the time the study was designed), and to analyse the factors associated with a lack of asthma control.This was a multicentre study in routine clinical practice performed in patients with uncontrolled asthma according to GINA 2010. At visit 1, we recorded demographics, asthma characteristics and spirometry. We assessed asthma control using GINA 2010 criteria and the Asthma Control Test (ACT). Treatment was optimised according to GINA 2010. At visit 2, 3 months later, we reassessed spirometry, asthma control and factors associated with failure to achieve control.We recruited 1299 patients with uncontrolled asthma (mean age 46.5±17.3 years, 60.7% women, 25.8% obese). The mean percentage of predicted forced expiratory volume in 1 s was 76.4±12.8% and the mean post-bronchodilator increase was 14.9±6.8%. We observed poor agreement between ACT and GINA 2010 when evaluating asthma control (kappa = -0.151). At visit 2, asthma in 71.2% of patients was still not fully controlled. Patients whose asthma remained uncontrolled were older, had a higher body mass index, greater disease severity, longer disease evolution and worse lung function.After treatment optimisation, most patients did not achieve optimal control according to GINA 2010. Risk factors for failure to achieve asthma control were time of disease evolution, severity, age, weight and lung function impairment (excluded in the GINA 2014).

Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug-dependent from nonsteroidal anti-inflammatory drug-independent food-induced anaphylaxis.

BACKGROUND: Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. OBJECTIVE: We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS: Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. RESULTS: Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS: Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.

Allergic rhinitis causes loss of smell in children: The OLFAPEDRIAL study.

BACKGROUND: The objective of the OLFAPEDRIAL study was to assess the olfactory dysfunction in allergic paediatric population, which has been scarcely studied. METHODS: Observational, cross-sectional and multicentre study evaluated the sense of smell in untreated allergic rhinitis (AR) paediatric patients aged 6-12 years. RESULTS: Forty-four per cent (551 of 1260) of children with AR reported smell dysfunction, with both loss of smell frequency (52.1%, p < 0.001) and intensity (0.75 ± 0.84, p < 0.0001) being more frequent in patients with persistent than intermittent AR (38.0% and 0.51 ± 0.73, respectively). In addition, both loss of smell frequency and intensity increased according to disease severity (m-ARIA classification) but always being significantly higher in persistent (p < 0.0001) than in intermittent AR. CONCLUSIONS: Children with allergic rhinitis present a mild-moderate loss of smell frequency and intensity which is clearly related to the disease duration and severity. The loss of smell can be considered, as in adults, a clinical marker of disease severity.